Noninvasive prenatal screening in twin pregnancies with cell-free DNA using the IONA test: a prospective multicenter study.
In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies. In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance. This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020. A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%-36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n=13; 95% confidence interval, 75-100), 0% for trisomy 18 (n=1; 95% confidence interval, 0-98), and 100% for trisomy 13 (n=1; 95% confidence interval, 3-100). The corresponding false-positive rates were 0% (95% confidence interval, 0-0.39), 0.10% (95% confidence interval, 0-0.58), and 0% (95% confidence interval, 0-0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n=74; 95% confidence interval, 90-99) and the false-positive rate was 0.09% (n=5598; 95% confidence interval, 0.03-0.19). The corresponding values for trisomy 18 were 82% (n=22; 95% confidence interval, 66-93) and 0.08% (n=4869; 95% confidence interval, 0.02-0.18), respectively. There were 5 cases of trisomy 13 and 3881 non-trisomy 13 pregnancies, resulting in a computed average detection rate of 80% and a false-positive rate of 0.13%. This large multicenter study confirms that cell-free DNA testing is the most accurate screening test for trisomy 21 in twin pregnancies, with screening performance similar to that in singletons and very low failure rates (0.31%). The predictive accuracy for trisomies 18 and 13 may be less. However, given the low false-positive rate, offering first-line screening with cell-free DNA to women with twin pregnancy is appropriate in our view and should be considered a primary screening test for trisomy 21 in twins.


Robustness of spiking Deep Belief Networks to noise and reduced bit precision of neuro-inspired hardware platforms.
Increasingly large deep learning architectures, such as Deep Belief Networks (DBNs) are the focus of current machine learning research and achieve state-of-the-art results in different domains. However, both training and execution of large-scale Deep Networks require vast computing resources, leading to high power requirements and communication overheads. The on-going work on design and construction of spike-based hardware platforms offers an alternative for running deep neural networks with significantly lower power consumption, but has to overcome hardware limitations in terms of noise and limited weight precision, as well as noise inherent in the sensor signal. This article investigates how such hardware constraints impact the performance of spiking neural network implementations of DBNs. In particular, the influence of limited bit precision during execution and training, and the impact of silicon mismatch in the synaptic weight parameters of custom hybrid VLSI implementations is studied. Furthermore, the network performance of spiking DBNs is characterized with regard to noise in the spiking input signal. Our results demonstrate that spiking DBNs can tolerate very low levels of hardware bit precision down to almost two bits, and show that their performance can be improved by at least 30% through an adapted training mechanism that takes the bit precision of the target platform into account. Spiking DBNs thus present an important use-case for large-scale hybrid analog-digital or digital neuromorphic platforms such as SpiNNaker, which can execute large but precision-constrained deep networks in real time.


Mechanisms of Gait Asymmetry Due to Push-Off Deficiency in Unilateral Amputees.
Unilateral lower-limb amputees exhibit asymmetry in many gait features, such as ground force, step time, step length, and joint mechanics. Although these asymmetries result from weak prosthetic-side push-off, there is no proven mechanistic explanation of how that impairment propagates to the rest of the body. We used a simple dynamic walking model to explore possible consequences of a unilateral impairment similar to that of a transtibial amputee. The model compensates for reduced push-off work from one leg by performing more work elsewhere, for example during the middle of stance by either or both legs. The model predicts several gait abnormalities, including slower forward velocity of the body center-of-mass during intact-side stance, greater energy dissipation in the intact side, and more positive work overall. We tested these predictions with data from unilateral transtibial amputees (N = 11) and nonamputee control subjects (N = 10) walking on an instrumented treadmill. We observed several predicted asymmetries, including forward velocity during stance phases and energy dissipation from the two limbs, as well as greater work overall. Secondary adaptations, such as to reduce discomfort, may exacerbate asymmetry, but these simple principles suggest that some asymmetry may be unavoidable in cases of unilateral limb loss.


Positive selection of natural autoreactive B cells.
Lymphocyte development is critically influenced by self-antigens. T cells are subject to both positive and negative selection, depending on their degree of self-reactivity. Although B cells are subject to negative selection, it has been difficult to test whether self-antigen plays any positive role in B cell development. A murine model system of naturally generated autoreactive B cells with a germ line gene-encoded specificity for the Thy-1 (CD90) glycoprotein was developed, in which the presence of self-antigen promotes B cell accumulation and serum autoantibody secretion. Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity.


Costs of early detection systems for epidemic malaria in highland areas of Kenya and Uganda.
Malaria epidemics cause substantial morbidity and mortality in highland areas of Africa. The costs of detecting and controlling these epidemics have not been explored adequately in the past. This study presents the costs of establishing and running an early detection system (EDS) for epidemic malaria in four districts in the highlands of Kenya and Uganda. An economic costing was carried out from the health service provider's perspective in both countries. Staff time for data entry and processing, as well as supervising and coordinating EDS activities at district and national levels was recorded and associated opportunity costs estimated. A threshold analysis was carried out to determine the number of DALYs or deaths that would need to be averted in order for the EDS to be considered cost-effective. The total costs of the EDS per district per year ranged between US$ 14,439 and 15,512. Salaries were identified as major cost-drivers, although their relative contribution to overall costs varied by country. Costs of relaying surveillance data between facilities and district offices (typically by hand) were also substantial. Data from Uganda indicated that 4% or more of overall costs could potentially be saved by switching to data transfer via mobile phones. Based on commonly used thresholds, 96 DALYs in Uganda and 103 DALYs in Kenya would need to be averted annually in each district for the EDS to be considered cost-effective. Results from this analysis suggest that EDS are likely to be cost-effective. Further studies that include the costs and effects of the health systems' reaction prompted by EDS will need to be undertaken in order to obtain comprehensive cost-effectiveness estimates.


Functional reorganization of the locomotor network in Parkinson patients with freezing of gait.
Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson's disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG- and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG- patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia.


A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.
ABT-288, a highly selective histamine-3 receptor antagonist, demonstrated efficacy across several preclinical cognitive domains, and safety in healthy subjects and elderly volunteers. Evaluate the efficacy and safety of ABT-288 in subjects with mild-to-moderate Alzheimer's dementia. The study used a randomized, double-blind, placebo- and active-controlled, parallel group design with pre-defined futility criteria to permit early study termination. A total of 242 subjects were randomized in an equal ratio to ABT-288 1 mg or 3 mg, donepezil 10 mg, or placebo once daily for 12 weeks. The primary efficacy endpoint was the change from baseline to final evaluation on the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. The study was prematurely terminated because futility criteria were met. Point estimates on the ADAS-Cog scores for both ABT-288 dose groups were numerically inferior to placebo but no statistical differences were detected. Donepezil demonstrated statistically significant improvement. Adverse events were generally mild and self-limiting. ABT-288 did not demonstrate efficacy in the symptomatic treatment of Alzheimer's dementia.


Comprehensive ascertainment of bleeding in patients prescribed different combinations of dual antiplatelet therapy (DAPT) and triple therapy (TT) in the UK: study protocol for three population-based cohort studies emulating 'target trials' (the ADAPTT Study).
'Real world' bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified. We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three 'target trials' in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study's main limitation-that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD. This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders. 76607611; Pre-results.


The chemopreventive potential of lycopene against atrazine-induced cardiotoxicity: modulation of ionic homeostasis.
People who drink water contaminated with atrazine (ATR) over many years can experience problems with their cardiovascular system. Lycopene (LYC) has been shown to exhibit cardiovascular disease preventive effects. However, chemopreventive potential of LYC against ATR-induced cardiotoxicity remains unclear. To determine the effects of ATR and/or LYC on heart, mice were treated with ATR (50 mg/kg or 200 mg/kg) and/or LYC (5 mg/kg) by intragastric administration for 21 days. Histopathological and biochemical analyses, including analysis of ion concentrations (Na(+), K(+), Ca(2+) and Mg(2+)), ATPases (Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase) activities and the transcription of their subunits, were performed on heart. The results revealed that ATR led to decreased Creative Kinase (CK) activity and increased histological alterations. Furthermore, a significant change in Na(+), K(+) and Ca(2+) content and the down-regulation of Na(+)-K(+)-ATPase and Ca(2+)-ATPase activities and the mRNA expression of their subunits were observed in ATR-exposed mice. Notably, supplementary LYC significantly protected the heart against ATR-induced damage. In conclusion, ATR induced cardiotoxicity by modulating cardiac ATPase activity and the transcription of its subunits, thereby triggering ionic disturbances. However, supplementary LYC significantly combated ATR-induced cardiotoxicity via the regulation of ATPase activity and subunit transcription. Thus, LYC exhibited a significant chemopreventive potential against ATR-induced cardiotoxicity.


NT-proBNP as a biomarker for hyperdynamic circulation in decompensated cirrhosis.
To assess NT-proBNP as a biomarker for hyperdynamic circulation in decompensated cirrhosis. Hyperdynamic circulation is common in decompensated cirrhosis. The previous studies reveal that N-terminal-proBNP (NT-proBNP) is elevated in cirrhosis. A prospective study involved 47 patients with decompensated cirrhosis. All of them underwent echocardiography with simultaneous measurement of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated. The concentration of NT-proBNP in blood was measured with enzyme-linked immunosorbent assay. In patients with decompensated cirrhosis, the concentration of NT-proBNP in blood directly correlated with end-diastolic volume (r=0.482; p<0.001), stroke volume (r= 0.566; p<0.001), cardiac output (r=0.556; p<0.001), volume of the left atrium (r=0.292; p=0.047), and inversely correlated with systemic vascular resistance (r=-0.538; p<0.001). There was no significant correlation between NT-proBNP and ejection fraction (p=0.083). Patients with hyperdynamic circulation have higher concentration of NT-proBNP (152÷476 pg/ml vs. 31÷133 pg/ml, p<0.001) regardless of the presence of diastolic dysfunction (p=0.222). According to ROC analysis, the best cut-off values for detection of hyperdynamic circulation in decompensated cirrhosis are considered to be 170.0 pg/ml of blood NT-proBNP, showing sensitivity and specificity of 72.0 and 86.4%, respectively. The positive and negative predictive value are 86.4% and 73.1%, AUC = 0.829 (0.709-0.949). NT-proBNP may serve as a non-invasive biomarker for hyperdynamic circulation in decompensated cirrhosis.


Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism.
Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.


Length and elasticity of side reins affect rein tension at trot.
This study investigated the horse's contribution to tension in the reins. The experimental hypotheses were that tension in side reins (1) increases biphasically in each trot stride, (2) changes inversely with rein length, and (3) changes with elasticity of the reins. Eight riding horses trotted in hand at consistent speed in a straight line wearing a bit and bridle and three types of side reins (inelastic, stiff elastic, compliant elastic) were evaluated in random order at long, neutral, and short lengths. Strain gauge transducers (240 Hz) measured minimal, maximal and mean rein tension, rate of loading and impulse. The effects of rein type and length were evaluated using ANOVA with Bonferroni post hoc tests. Rein tension oscillated in a regular pattern with a peak during each diagonal stance phase. Within each rein type, minimal, maximal and mean tensions were higher with shorter reins. At neutral or short lengths, minimal tension increased and maximal tension decreased with elasticity of the reins. Short, inelastic reins had the highest maximal tension and rate of loading. Since the tension variables respond differently to rein elasticity at different lengths, it is recommended that a set of variables representing different aspects of rein tension should be reported.


Transforming Growth Factor-β1 Induces Endothelial-to-Mesenchymal Transition via Akt Signaling Pathway in Renal Transplant Recipients with Chronic Allograft Dysfunction.
BACKGROUND Chronic allograft dysfunction (CAD) is the major cause of chronic loss of allograft in kidney transplant recipients. Kidney interstitial fibrosis is identified to be strongly associated with CAD in kidney transplantation. Recently, endothelial-to-mesenchymal transition (EndMT) has been identified as one of the potential mechanisms in kidney interstitial fibrosis. MATERIAL AND METHODS Kidney tissue samples from 25 renal transplant recipients (RTRs) with CAD and healthy volunteers were collected for HE (hematoxylin-eosin), Masson trichrome, and immunohistochemical staining, and indirect immunofluorescence double-staining assay. Moreover, human umbilical vascular endothelial cells (HUVECs) were cultured and treated with TGF-β1 at different doses or intervals. The protein expressions of α-SMA and CD31 were determined by Western blot assay. Furthermore, potential signaling pathways involved in EndMT induced by TGF-β1were also investigated by Western blotting. RESULTS Typical interstitial fibrosis was observed in transplanted renal tissues from the CAD group. We also found a significant increase of TGF-β1 expression in renal tissues from RTRs with CAD compared with the normal group. Moreover, significant over-expressions of α-SMA, collagen-I, and collagen-III and under-expression of CD31 were detected in kidney specimens of the CAD group. Similar expressive tendencies of α-SMA and CD31 proteins were found in HUVECs treated with TGF-β1 in both time-dependent and dose-dependent manners. The activation of the Akt signaling pathway was found in HUVECs induced by TGF-β1 and selective inhibitors. CONCLUSIONS EndMT was observed in kidney tissues from RTRs with CAD, and TGF-β1 can induce the process of EndMT in both time-dependent and does-dependent manners through the Akt signaling pathway.


Tasks, multitasking and interruptions among the surgical team in an operating room: a prospective observational study.
The work context of the operating room (OR) is considered complex and dynamic with high cognitive demands. A multidimensional view of the complete preoperative and intraoperative work process of the surgical team in the OR has been sparsely described. The aim of this study was to describe the type and frequency of tasks, multitasking, interruptions and their causes during surgical procedures from a multidimensional perspective on the surgical team in the OR. Prospective observational study using the Work Observation Method By Activity Timing tool. An OR department at a county hospital in Sweden. OR nurses (ORNs) (n=10), registered nurse anaesthetists (RNAs) (n=8) and surgeons (n=9). The type, frequency and time spent on specific tasks, multitasking and interruptions were measured. From a multidimensional view, the surgical team performed 64 tasks per hour. Communication represented almost half (45.7%) of all observed tasks. Concerning task time, direct care dominated the surgeons' and ORNs' intraoperative time, while in RNAs' work, it was intra-indirect care. In total, 48.2% of time was spent in multitasking and was most often observed in ORNs' and surgeons' work during communication. Interruptions occurred 3.0 per hour, and the largest proportion, 26.7%, was related to equipment. Interruptions were most commonly followed by professional communication. The surgical team constantly dealt with multitasking and interruptions, both with potential impact on workflow and patient safety. Interruptions were commonly followed by professional communication, which may reflect the interactions and constant adaptations in a complex adaptive system. Future research should focus on understanding the complexity within the system, on the design of different work processes and on how teams meet the challenges of a complex adaptive system. 2016/264.


17-Beta Hydroxysteroid Dehydrogenase 13 Is a Hepatic Retinol Dehydrogenase Associated With Histological Features of Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. A single-nucleotide polymorphism (SNP), rs6834314, was associated with serum liver enzymes in the general population, presumably reflecting liver fat or injury. We studied rs6834314 and its nearest gene, 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13), to identify associations with histological features of NAFLD and to characterize the functional role of HSD17B13 in NAFLD pathogenesis. The minor allele of rs6834314 was significantly associated with increased steatosis but decreased inflammation, ballooning, Mallory-Denk bodies, and liver enzyme levels in 768 adult Caucasians with biopsy-proven NAFLD and with cirrhosis in the general population. We found two plausible causative variants in the HSD17B13 gene. rs72613567, a splice-site SNP in high linkage with rs6834314 (r2 = 0.94) generates splice variants and shows a similar pattern of association with NAFLD histology. Its minor allele generates simultaneous expression of exon 6-skipping and G-nucleotide insertion variants. Another SNP, rs62305723 (encoding a P260S mutation), is significantly associated with decreased ballooning and inflammation. Hepatic expression of HSD17B13 is 5.9-fold higher (P = 0.003) in patients with NAFLD. HSD17B13 is targeted to lipid droplets, requiring the conserved amino acid 22-28 sequence and amino acid 71-106 region. The protein has retinol dehydrogenase (RDH) activity, with enzymatic activity dependent on lipid droplet targeting and cofactor binding site. The exon 6 deletion, G insertion, and naturally occurring P260S mutation all confer loss of enzymatic activity. Conclusion: We demonstrate the association of variants in HSD17B13 with specific features of NAFLD histology and identify the enzyme as a lipid droplet-associated RDH; our data suggest that HSD17B13 plays a role in NAFLD through its enzymatic activity.


The prevalence of hypertension among the elderly in patients in Al-Zahra Hospital, Isfahan, Iran.
In this study, we discussed aging and common diseases associated with it which can lead to hospitalization. Hypertension was also evaluated as one of the factors affecting morbidity and mortality in elderly people. In this cross-sectional study, data was collected using checklists and extracting information from medical records in Al-Zahra Hospital (Isfahan, Iran). Data was then analyzed using descriptive statistics according to the research questions in SPSS. A total number of 11,018 people aged 60-99 years were studied. Cardiovascular diseases were the most common cause of hospitalization [2063 patients (18.7%)]. In patients with cardiovascular diseases, 84 were suffering from hypertension, 76 had primary hypertension, 7 had hypertensive heart disease with or without congestive heart failure, and 1 had secondary hypertension. Among all hypertensive patients, there were 37 males (44.05%) and 47 females (55.95%). Moreover, 34 people aged 60-69, 30 aged 70-79, 18 aged 80-89 and 2 aged 90-99 years. Duration of hospitalization was less than 1 day for 12 people, 1-2 days for 27, 3-5 days for 25, 6-10 days for 14, 15-11 days for 6, and more than 15 days for 1 person. Prevention and treatment of hypertension is important in order to control this disease. Untreated or poorly/untimely controlled hypertension would thus leave permanent side effects. It may thus leave sustained side effects if remain untreated or poorly/untimely controlled. However, people with hypertension were in minority in our study. Therefore, more research in this field with larger sample size is necessary for further identification of factors affecting quality of life in elderly people.


Role of CT in assessing pleural malignancy prior to thoracoscopy.
The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as 'malignant' in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.


The effects of expression: how providing emotional support online improves cancer patients' coping strategies.
Emotional support has traditionally been conceived as something a breast cancer patient receives. However, this framework may obscure a more complex process, facilitated by the emerging social media environment, which includes the effects of composing and sending messages to others. Accordingly, this study explores the effects of expression and reception of emotional support messages in online groups and the importance of bonding as a mediator influencing the coping strategies of breast cancer patients. Data were collected as part of two National Cancer Institute-funded randomized clinical trials. Eligible subjects were within 2 months of diagnosis of primary breast cancer or recurrence. Expression and reception of emotionally supportive messages were tracked and coded for 237 breast cancer patients. Analysis resulted from merging 1) computer-aided content analysis of discussion posts, 2) action log analysis of system use, and 3) longitudinal survey data. As expected, perceived bonding was positively related to all four coping strategies (active coping: β = 0.251, P = .000; positive reframing: β = 0.288, P = .000; planning: β = 0.213, P = .006; humor: β = 0.159, P = .009). More importantly, expression (γ = 0.138, P = .027), but not reception (γ = -0.018, P = .741), of emotional support increases perceived bonding, which in turn mediates the effects on patients' positive coping strategies. There is increasing importance for scholars to distinguish the effects of expression from reception to understand the processes involved in producing psychosocial benefits. This study shows that emotional support is more than something cancer patients receive; it is part of an active, complex process that can be facilitated by social media.


Characterization of the regulatory mechanisms of activating transcription factor 3 by hypertrophic stimuli in rat cardiomyocytes.
Activating transcription factor 3 (ATF3) is a stress-activated immediate early gene suggested to have both detrimental and cardioprotective role in the heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli and ATF3 downstream targets in rat cardiomyocytes. When neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM) and mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1 hour. Inhibition of extracellular signal-regulated kinase (ERK) by PD98059 decreased ET-1- and stretch-induced increase of ATF3 protein but not ATF3 mRNA levels, whereas protein kinase A (PKA) inhibitor H89 attenuated both ATF3 mRNA transcription and protein expression in response to ET-1 and stretch. To characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen-activated protein kinase (MAPK) signaling was investigated using a gain-of-function approach. Adenoviral overexpression of p38α, but not p38β, increased ATF3 mRNA and protein levels as well as DNA binding activity. To investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the mRNA transcription of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1), and enhanced nuclear factor-κB (NF-κB) and Nkx-2.5 DNA binding activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart by direct intramyocardial adenovirus-mediated ATF3 gene delivery. These data demonstrate that ATF3 activation by ET-1 and mechanical stretch is partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is involved in ATF3 activation exclusively through p38α isoform. ATF3 activation caused induction of modulators of the inflammatory response NF-κB and Nkx-2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6 and PAI-1, suggesting cardioprotective role for ATF3 in the heart.


Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy.
Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.


Frailty and cardiac rehabilitation: A call to action from the EAPC Cardiac Rehabilitation Section.
Frailty is a geriatric syndrome characterised by a vulnerability status associated with declining function of multiple physiological systems and loss of physiological reserves. Two main models of frailty have been advanced: the phenotypic model (primary frailty) or deficits accumulation model (secondary frailty), and different instruments have been proposed and validated to measure frailty. However measured, frailty correlates to medical outcomes in the elderly, and has been shown to have prognostic value for patients in different clinical settings, such as in patients with coronary artery disease, after cardiac surgery or transvalvular aortic valve replacement, in patients with chronic heart failure or after left ventricular assist device implantation. The prevalence, clinical and prognostic relevance of frailty in a cardiac rehabilitation setting has not yet been well characterised, despite the increasing frequency of elderly patients in cardiac rehabilitation, where frailty is likely to influence the onset, type and intensity of the exercise training programme and the design of tailored rehabilitative interventions for these patients. Therefore, we need to start looking for frailty in elderly patients entering cardiac rehabilitation programmes and become more familiar with some of the tools to recognise and evaluate the severity of this condition. Furthermore, we need to better understand whether exercise-based cardiac rehabilitation may change the course and the prognosis of frailty in cardiovascular patients.


Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma.
Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case-control data in male subjects. Cases were selected from a French case-control study conducted in 1987-1993 and the French National Mesothelioma Surveillance Program in 1998-2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case-control study, underline the need to take into account the temporal pattern of exposure on risk assessment.


Statin exposure is associated with decreased asthma-related emergency department visits and oral corticosteroid use.
Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects. To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort. Statin users aged 31 years or greater with asthma were identified from the Population-Based Effectiveness in Asthma and Lung population, which includes data from five health plans. Statin exposure and asthma exacerbations were assessed over a 24-month observation period. Statin users with a statin medication possession ratio greater than or equal to 80% were matched to non-statin users by age, baseline asthma therapy, site of enrollment, season at baseline, and propensity score, which was calculated based on patient demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as two or more oral corticosteroid dispensings, asthma-related emergency department visits, or asthma-related hospitalizations. The association between statin exposure and each of the three outcome measures was assessed using conditional logistic regression. Of the 14,566 statin users, 8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson conditions that remained unbalanced after matching, among statin users, statin exposure was associated with decreased odds of having asthma-related emergency department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.77; P < 0.0001) and two or more oral corticosteroid dispensings (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04). There were no differences in asthma-related hospitalizations (OR, 0.91; 95% CI, 0.66-1.24; P = 0.52). Among statin users with asthma, statin exposure was associated with decreased odds of asthma-related emergency department visits and oral corticosteroid dispensings.


Pattern of sexual behavior among people in a rural area of Bihar: A qualitative study on wives of migrant workers.
Population mobility and migration are important processes of human life. It affects broad range of sociocultural parameters. Mobility increases personal interaction and exposure to sexual partners from high-risk group. Although traditional Indian value prohibits premarital or extramarital sexual activities, but this aspect has not been explored in migrant workers. It was a qualitative study based on indepth interview of participants. The participants were wives of migrant workers. Indepth interviews were conducted by two female field interviewers recruited for the study. A total of 24 study subjects were recruited for the study. An indepth interview guide was prepared which mainly focused on sexual behavior, including premarital, marital, and extramarital, quality of marital relationship, gender roles, peer networks, substance abuse, work-related activities, etc., The transcripts were analyzed in NVIVO and themes were generated. The premarital sex was more common in boys than girls. It is more common in the same age group and has increased in the recent years. Various reasons were cited in relation to premarital sex in rural areas like love affair, delayed marriage, watching bad movies, bad company, allurement for gifts money, etc., Some women had opinion that males belonging to affluent and powerful families had tendency to enjoy sex with other women within and outside village. The major themes which emerged from the study were the sexual activity, type of sexual partners, reasons for multiple sexual partner, and risky and nonrisky sexual activity. The findings of the study provided insights to design and conduct a larger and more representative quantitative study among the wives of migrant workers to understand the dynamic combination of biomedical, behavioral, and sociocultural factors that may influence transmission of infection within marriage.


Linking flowability and granulometry of lactose powders.
The flowing properties of 10 lactose powders commonly used in pharmaceutical industries have been analyzed with three recently improved measurement methods. The first method is based on the heap shape measurement. This straightforward measurement method provides two physical parameters (angle of repose αr and static cohesive index σr) allowing to make a first screening of the powder properties. The second method allows to estimate the rheological properties of a powder by analyzing the powder flow in a rotating drum. This more advanced method gives a large set of physical parameters (flowing angle αf, dynamic cohesive index σf, angle of first avalanche αa and powder aeration %ae) leading to deeper interpretations. The third method is an improvement of the classical bulk and tapped density measurements. In addition to the improvement of the measurement precision, the densification dynamics of the powder bulk submitted to taps is analyzed. The link between the macroscopic physical parameters obtained with these methods and the powder granulometry is analyzed. Moreover, the correlations between the different flowability indexes are discussed. Finally, the link between grain shape and flowability is discussed qualitatively.


Visceral afferent neuropathy in diabetic gastroparesis.
To determine whether a lack of symptoms in diabetic patients with gastrointestinal motility disorders is associated with visceral afferent neuropathy. We investigated cerebral evoked potentials (EPs) after esophageal stimulation in 10 patients with motor dysfunction of the gastrointestinal tract and in 10 healthy control subjects. All patients had insulin-dependent diabetes mellitus (5 men, 5 women, age range 31-60 yr, diabetes duration 8-36 yr, 10 of 10 with polyneuropathy, 6 of 10 with cardiac autonomic neuropathy). Their esophageal and gastric motor disorders had been diagnosed by scintigraphy, and gastrointestinal stenosis had been excluded by gastroscopy. Only 2 patients had severe symptoms, whereas 6 patients complained of minor discomfort (distension, bloating), and 2 patients were symptom free. EPs were recorded after electrical stimulation of the esophagus (32 cm from the incisors) at intensity just above the perception threshold. All control subjects exhibited regular EPs at 0.1 ms/30 mA stimulation intensity. In 6 diabetic patients, no EPs were detected at 0.1 and 0.3 ms/30 mA, and the perception thresholds were significantly elevated. In 4 patients with normal perception threshold, EPs of regular shape but decreased amplitude were recorded. These patients had mild or severe gastroparetic complaints. These data show for the first time an association between a lack of symptoms in diabetic gastrointestinal motility disorders and visceral afferent neuropathy.


Numerical evaluation of bioaccumulation and depuration kinetics of PAHs in Mytilus galloprovincialis.
Polycyclic aromatic hydrocarbons (PAHs) are important organic pollutants in the aquatic environment due to their persistence and bioaccumulation potential both in organisms and in sediments. Benzo(a)anthracene (BaA) and phenanthrene (PHE), which are in the priority pollutant list of the U.S. EPA (Environmental Protection Agency), are selected as model compounds of the present study. Bioaccumulation and depuration experiments with local Mediterranean mussel species, Mytilus galloprovincialis were used as the basis of the study. Mussels were selected as bioindicator organisms due to their broad geographic distribution, immobility and low enzyme activity. Bioaccumulation and depuration kinetics of selected PAHs in Mytilus galloprovincialis were described using first order kinetic equations in a three compartment model. The compartments were defined as: (1) biota (mussel), (2) surrounding environment (seawater), and (3) algae (Phaeodactylum tricornutum) as food source of the mussels. Experimental study had been performed for three different concentrations. Middle concentration of the experimental data was used as the model input in order to represent other high and low concentrations of selected PAHs. Correlations of the experiment and model data revealed that they are in good agreement. Accumulation and depuration trend of PAHs in mussels regarding also the durations can be estimated effectively with the present study. Thus, this study can be evaluated as a supportive tool for risk assessment in addition to monitoring studies.


Predictors of Mortality in Acute Ischemic Stroke Intervention: Analysis of the North American Solitaire Acute Stroke Registry.
Failure to recanalize predicts mortality in acute ischemic stroke. In the North American Solitaire Acute Stroke registry, we investigated parameters associated with mortality in successfully recanalized patients. Logistic regression was used to evaluate baseline characteristics and recanalization parameters for association with 90-day mortality. A multivariable model was developed based on backward selection with retention criteria of P<0.05 from factors with at least marginal significance (P≤0.10), then refit to minimize the number of excluded cases (missing data). Successfully recanalized patients had lower mortality (25.2% [59/234] versus 46.9% [38/81] P<0.001). There was no difference in symptomatic intracranial hemorrhage between patients with successful versus failed recanalization (9% [21/234] versus 14% [11/79]; P=0.205). However, mortality was significantly higher in patients with symptomatic intracranial hemorrhage (72% [23/32] versus 26% [73/281]; P<0.001). Proximal occlusion (internal carotid artery or vertebrobasilar), initial National Institutes of Health Stroke Scale≥18, use of rescue therapy (P<0.05), and 3+ passes (P<0.10) were associated with mortality in recanalized patients. In the multivariate model with good predictive power (c index=0.72), proximal occlusion, initial National Institutes of Health Stroke Scale≥18, and use of rescue therapy remained significant independent predictors of 90-day mortality. Failure to recanalize and presence of symptomatic intracranial hemorrhage resulted in increased mortality. Despite successful recanalization, proximal occlusion, high National Institutes of Health Stroke Scale, and need for rescue therapy were predictors of mortality.


Primary Myxoid Liposarcoma of the Lower Back in an Adult Female Patient: An Extremely Rare Presentation.
Myxoid liposarcoma is the second most common type of liposarcoma that typically presents in the lower extremities and has a predilection for men. Manifestation of this tumor in the lower back is rare. We report the first known case of an adult woman presenting with a soft tissue mass in her lower back. Following excision and further workup, the mass was positive for rearrangements of the DDIT3 (CHOP) gene at the 12q13 locus, consistent with the diagnosis of a myxoid liposarcoma. The tumor was noted to be intramuscular and extended into the margins, requiring re-excision at the previous resection site. Biopsy of the re-excised area was negative for evidence of residual myxoid liposarcoma. We report this case to highlight the importance of considering myxoid liposarcoma as a differential diagnosis in soft tissue masses presenting in the lower back.


Support surfaces for the treatment and prevention of pressure ulcers: a systematic literature review.
Changes in technology have resulted in a lack of clarity regarding the comparative effectiveness between active and reactive support surfaces in the prevention and treatment of pressure ulcers (PUs). The purpose of this literature review was to evaluate the comparative effectiveness of active and reactive mattresses for prevention and treatment of PUs. A literature search was completed using CINAHL, Medline Plus, Scopus, Cochrane Library and PubMed databases, as well as reference lists. A temporal limiter was placed excluding studies published before 2000 due to changes in care standards and support surface technology. Of the 33 articles included, nine were systematic/literature reviews and 24 were randomised controlled trials (RCTs). There was a consensus that pressure mattresses are an effective prevention and treatment strategy, however comparisons of the two types were often inconclusive or conflicting. Studies were conducted in acute, sub-acute or residential facilities, with no studies in a domiciliary setting. The majority of studies were rated as moderate quality with significant methodological limitations. Further research is needed to investigate the use of support surfaces in a domiciliary setting with an appropriate methodology aimed at minimising the limitations described in the existing literature.


Expression-system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity.
Recombinant expression systems differ in the type of glycosylation they impart on expressed antigens such as the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, potentially affecting their biological properties. We performed head-to-head antigenic, immunogenic and molecular profiling of two distantly related Env surface (gp120) antigens produced in different systems: (a) mammalian (293 FreeStyle cells; 293F) cells in the presence of kifunensine, which impart only high-mannose glycans; (b) insect cells (Spodoptera frugiperda, Sf9), which confer mainly paucimannosidic glycans; (c) Sf9 cells recombinant for mammalian glycosylation enzymes (Sf9 Mimic), which impart high-mannose, hybrid and complex glycans without sialic acid; and (d) 293F cells, which impart high-mannose, hybrid and complex glycans with sialic acid. Molecular models revealed a significant difference in gp120 glycan coverage between the Sf9-derived and wild-type mammalian-cell-derived material that is predicted to affect ligand binding sites proximal to glycans. Modeling of solvent-exposed surface electrostatic potentials showed that sialic acid imparts a significant negative surface charge that may influence gp120 antigenicity and immunogenicity. Gp120 expressed in systems that do not incorporate sialic acid displayed increased ligand binding to the CD4 binding and CD4-induced sites compared to those expressed in the system that do, and imparted other more subtle differences in antigenicity in a gp120 subtype-specific manner. Non-sialic-acid-containing gp120 was significantly more immunogenic than the sialylated version when administered in two different adjuvants, and induced higher titers of antibodies competing for CD4 binding site ligand-gp120 interaction. These findings suggest that non-sialic-acid-imparting systems yield gp120 immunogens with modified antigenic and immunogenic properties, considerations that should be considered when selecting expression systems for glycosylated antigens to be used for structure-function studies and for vaccine use.


Surfaces modified with nanometer-thick silver-impregnated polymeric films that kill bacteria but support growth of mammalian cells.
Silver is widely used as a biocidal agent in ointments and wound dressings. However, it has also been associated with tissue toxicity and impaired healing. In vitro characterization has also revealed that typical loadings of silver employed in ointments and dressings (approximately 100 microg/cm(2)) lead to cytotoxicity. In this paper, we report the results of an initial study that sought to determine if localization of carefully controlled loadings of silver nanoparticles within molecularly thin films immobilized on surfaces can lead to antimicrobial activity without inducing cytotoxicity. Polymeric thin films of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) were prepared by layer-by-layer deposition and loaded with approximately 0.4 microg/cm(2) to approximately 23.6 microg/cm(2) of silver nanoparticles. Bacterial killing efficiencies of the silver-loaded films were investigated against Staphylococcus epidermidis, a gram-positive bacterium, and it was determined that as little as approximately 0.4 microg/cm(2) of silver in the polymeric films caused a reduction of 6log(10)CFU/mL (99.9999%) bacteria in suspensions incubated in contact with the films (water-borne assays). Significantly, whereas the antibacterial films containing high loadings of silver were found to be toxic to a murine fibroblast cell line (NIH-3T3), the polymeric films containing approximately 0.4 microg/cm(2) of silver were not toxic and allowed attachment, and growth of the mammalian cells. Thus, the results of this study go beyond prior reports by identifying silver-impregnated, polymeric thin films that are compatible with in vitro mammalian cell culture yet exhibit antibacterial activity. These results support the hypothesis that localization of carefully controlled loadings of silver nanoparticles within molecularly thin polymeric films can lead to antimicrobial activity without cytotoxicity. More broadly, this strategy of modifying surfaces with minimal loadings of bioactive molecules indicates the basis of approaches that may permit management of microbial burden in wound beds without impairment of wound healing.


Echinococcus multilocularis in Austrian foxes from 1991 until 2004.
The prevalence rates of Echinococcus multilocularis in foxes (n=5600) evaluated in several Austrian surveys conducted between 1991 and 2004 were analysed for spatial and temporal differences. Data from early studies (1993-1997) in which the intestinal scraping technique (IST) was utilized were compared with data from recent (1999-2004) investigations, which made use of the shaking in a vessel technique (SVT), and it was assessed whether or not the infection rates of Austrian foxes had increased between the investigated intervals. In total, data from 85 districts are presented and both the retrospective and recent data are available from 39 of these districts. A Bayesian hierarchical model of parasite prevalences is presented which (i) accounts for differences in the sensitivity of IST and SVT, (ii) incorporates spatial auto-correlation between neighbouring districts, (iii) investigates the possibility of a temporal shift in the infection status of foxes, and (iv) quantifies uncertainty at each level of the model. The national average prevalence rates in the mid-1990s and at the turn of the millennium were 2.4% (95% confidence intervals 1.1-4.8) and 3.9% (95% confidence intervals 1.5-8.4) respectively. Above average prevalence rates were observed in the western and the northern parts of the country. Evidence is also presented for a temporal augmentation of the prevalence rates in some districts in the northern and eastern parts of the country. These findings are in concordance with several investigations in other European states where both newly emerged areas and elevated levels of transmission in existing endemic areas have been found. None of the districts investigated here showed significant evidence of a drop in prevalence.


Clipping Versus Coiling in Ruptured Basilar Apex Aneurysms: A Meta-Analysis.
To assess the results, effectiveness, safety, and potentials of coiling and clipping of ruptured basilar apex aneurysms. Included in this study were articles comparisons of outcomes of endovascular coiling and clipping of ruptured basilar apex aneurysms, published in the full-text form (from 1960 to March 31, 2020). Collected variables included: first author?s name, country, study period covered, publication year, the total number of patients and follow-up, the early postoperative mortality rate (PostOp-Mo) (30 days from the selecting treatment), permanent neurological deficit (PND), late mortality (LateMo) (after 1 month) and re-intervention (ReInt) (requiring surgery or coiling), for both groups. Outcomes reported by the eligible articles should be evaluated at least 6 months after subarachnoid hemorrhage or intervention (clipping or coiling). After the preliminary searching, 210 articles were established to be nominees for further investigation. After the application of exclusion and inclusion criteria, there were 9 eligible articles left. The total number of patients was 582 (241 in the clipping group and 341 in coiling). Regarding PostOp-Mo, PND, and LateMo the final results demonstrated no potential significant difference between the two groups. Regarding the subgroup of patients with the ReInt the findings illustrated a statistically significant difference among the two groups [OR 2.33, CI 95%, (1.62? 3.09), Chi2=0.59 and p=0.001] with no heterogeneity (p=0.79 and I2=-69.27%). Management complications, recurrences, and reintervention are considerably more frequent in endovascularly treated BX aneurysms.


Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial.
Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States. HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy individuals age 18-65 years at low HIV risk were randomized (3:1) to receive CAB or placebo (PBO). In the initial oral phase, participants received 1 daily oral tablet (CAB or PBO) for 4 weeks. Those without safety concerns in the oral phase continued and received injections in the injection phase (Cohort 1: 3 injections of CAB LA 800 mg or 0.9% saline as PBO IM every 12 weeks for 3 injection cycles; Cohort 2: CAB LA 600 mg or PBO IM for 5 injection cycles; the first 2 injections in Cohort 2 were separated by 4 weeks, the rest by 8 weeks). The primary analysis included weeks 5 to 41 of study participation, encompassing the injection phase. The cohorts were enrolled sequentially. Primary outcomes were safety and tolerability. Secondary outcomes included pharmacokinetics and events occurring during the oral and injection phases. Between February 9, 2015, and May 27, 2016, the study screened 443 individuals and enrolled 110 participants in Cohort 1 and 89 eligible participants in Cohort 2. Participant population characteristics were as follows: 66% female at birth; median age 31 years; 27% non-Hispanic white, 41% non-Hispanic black, 24% Hispanic/Latino, 3% Asian, and 6% mixed/other; and 6 transgender men and 1 transgender woman. Twenty-two (11%) participants discontinued the oral study product; 6 of these were for clinical or laboratory adverse events (AEs). Of those who received at least 1 CAB LA injection, 80% of Cohort 1 and 92% of Cohort 2 participants completed all injections; injection course completion rates were not different from those in the PBO arm. Injection site reactions (ISRs) were common (92% of Cohort 1 and 88% of Cohort 2 participants who received CAB LA reported any ISR). ISRs were mostly Grade 1 (mild) to Grade 2 (moderate), and 1 ISR event (Cohort 1) led to product discontinuation. Grade 2 or higher ISRs were the only AEs reported more commonly among CAB LA recipients than PBO recipients. Two Grade 3 (severe) ISRs occurred in CAB recipients, 1 in each cohort, but did not lead to product discontinuation in either case. Seven incident sexually transmitted infections were diagnosed in 6 participants. One HIV infection occurred in a participant 48 weeks after last injection of CAB LA: CAB was not detectable in plasma both at the time of first reactive HIV test and at the study visit 12 weeks prior to the first reactive test. Participants in Cohort 2 (unlike Cohort 1) consistently met prespecified pharmacokinetic targets of at least 95% of participants maintaining CAB trough concentrations above PA-IC90, and 80% maintaining trough concentrations above 4× PA-IC90. Study limitations include a modest sample size, a short course of injections, and a low-risk study population. In this study, CAB LA was well tolerated at the doses and dosing intervals used. ISRs were common, but infrequently led to product discontinuation. CAB LA 600 mg every 8 weeks met pharmacokinetic targets for both male and female study participants. The safety and pharmacokinetic results observed support the further development of CAB LA, and efficacy studies of CAB LA for HIV treatment and prevention are in progress. ClinicalTrials.gov Registry: ClinicalTrials.gov Trial number: NCT02178800.


Reducing violence risk in persons with schizophrenia: olanzapine versus risperidone.
This study prospectively examined the effectiveness of treatment with olanzapine versus risperidone in reducing violent behavior among patients with schizophrenia under "usual care" conditions in the community. Participants were 124 adults with DSM-IV-diagnosed schizophrenia-spectrum disorders receiving services in public-sector mental health systems in North Carolina. After enrollment (1997-1999), subjects were followed for 3 years in an observational study with interviews at 6-month intervals to assess treatment, clinical outcomes, and violent behavior. Rates of violence were compared over time between periods of first switch to olanzapine or risperidone and periods following at least 1 year of treatment with each of these medications. The study found that remaining on olanzapine for 1 year or more significantly lowered violence risk compared to first switch period, but no significant change in violence risk was found for subjects remaining on risperidone for 1 year or more. These results were obtained using multivariable time-series analysis controlling for salient demographic and clinical covariates. This study found that, in the complex "real world" settings where persons with schizophrenia reside, long-term treatment with olanzapine confers some advantage over risperidone in reducing violence risk. This advantage appears to be at least in part an indirect effect, via improvement in adherence with treatment. Specifically, adherence with prescribed medication was found to mediate the association between olanzapine treatment and reduced violent behavior.


On the debris-level origins of adhesive wear.
Every contacting surface inevitably experiences wear. Predicting the exact amount of material loss due to wear relies on empirical data and cannot be obtained from any physical model. Here, we analyze and quantify wear at the most fundamental level, i.e., wear debris particles. Our simulations show that the asperity junction size dictates the debris volume, revealing the origins of the long-standing hypothesized correlation between the wear volume and the real contact area. No correlation, however, is found between the debris volume and the normal applied force at the debris level. Alternatively, we show that the junction size controls the tangential force and sliding distance such that their product, i.e., the tangential work, is always proportional to the debris volume, with a proportionality constant of 1 over the junction shear strength. This study provides an estimation of the debris volume without any empirical factor, resulting in a wear coefficient of unity at the debris level. Discrepant microscopic and macroscopic wear observations and models are then contextualized on the basis of this understanding. This finding offers a way to characterize the wear volume in atomistic simulations and atomic force microscope wear experiments. It also provides a fundamental basis for predicting the wear coefficient for sliding rough contacts, given the statistics of junction clusters sizes.


Using the Model for Improvement to implement the Critical-Care Pain Observation Tool in an adult intensive care unit.
Managing pain is challenging in the intensive care unit (ICU) as often patients are unable to self-report due to the effects of sedation required for mechanical ventilation. Minimal sedative use and the utilisation of analgesia-first approaches are advocated as best practice to reduce unwanted effects of oversedation and poorly managed pain. Despite evidence-based recommendations, behavioural pain assessment tools are not readily implemented in many critical care units. A local telephone audit conducted in April 2017 found that only 30% of Scottish ICUs are using these validated pain instruments. The intensive care unit (ICU) at Raigmore Hospital, NHS Highland, initiated a quality improvement (QI) project using the Model for Improvement (MFI) to implement an analgesia-first approach utilising a validated and reliable behavioural pain assessment tool, namely the Critical-Care Pain Observation Tool (CPOT). Over a six-month period, the project deployed QI tools and techniques to test and implement the CPOT. The process measures related to (i) the nursing staff's reliability to assess and document pain scores at least every four hours and (ii) to treat behavioural signs of pain or CPOT scores ≥ 3 with a rescue bolus of opioid analgesia. The findings from this project confirm that the observed trends in both process measures had reduced over time. Four hourly assessments of pain had increased to 89% and the treatment of CPOT scores ≥3 had increased to 100%.


Asymptomatic iatrogenic right coronary artery dissection with spontaneous resolution. A case report.
A young woman with angiographically normal coronary arteries had asymptomatic iatrogenic catheter-induced dissection of her right coronary artery which was managed conservatively. Because of continuing chest pain despite therapy, over a year later she again underwent selective coronary arteriography; a Softip cardiovascular catheter (Angiomedics Inc., Minneapolis) was used without complication. This may be the first report of use of this catheter after previous iatrogenic coronary artery dissection caused by a more conventional type. It is also the first time that this catheter was employed in the RSA. The use of a Softip cardiovascular catheter may significantly reduce this complication of a common coronary angiography.


Relating amino acid sequence to phenotype: analysis of peptide-binding data.
We illustrate data analytic concerns that arise in the context of relating genotype, as represented by amino acid sequence, to phenotypes (outcomes). The present application examines whether peptides that bind to a particular major histocompatibility complex (MHC) class I molecule have characteristic amino acid sequences. However, the concerns identified and addressed are considerably more general. It is recognized that simple rules for predicting binding based solely on preferences for specific amino acids in certain (anchor) positions of the peptide's amino acid sequence are generally inadequate and that binding is potentially influenced by all sequence positions as well as between-position interactions. The desire to elucidate these more complex prediction rules has spawned various modeling attempts, the shortcomings of which provide motivation for the methods adopted here. Because of (i) this need to model between-position interactions, (ii) amino acids constituting a highly (20) multilevel unordered categorical covariate, and (iii) there frequently being numerous such covariates (i.e., positions) comprising the sequence, standard regression/classification techniques are problematic due to the proliferation of indicator variables required for encoding the sequence position covariates and attendant interactions. These difficulties have led to analyses based on (continuous) properties (e.g., molecular weights) of the amino acids. However, there is potential information loss in such an approach if the properties used are incomplete and/or do not capture the mechanism underlying association with the phenotype. Here we demonstrate that handling unordered categorical covariates with numerous levels and accompanying interactions can be done effectively using classification trees and recently devised bump-hunting methods. We further tackle the question of whether observed associations are attributable to amino acid properties as well as addressing the assessment and implications of between-position covariation.


Human LAP+GARP+FOXP3+ regulatory T cells attenuate xenogeneic graft versus host disease.
Adoptive transfer of regulatory T cells (FOXP3+ Tregs) has been developed as a potential curative immune therapy to prevent and treat autoimmune and graft-versus-host diseases (GVHD). A major limitation that has hindered the use of Treg immunotherapy in humans is the difficulty of consistently isolating and obtaining highly purified Tregs after ex vivo expansion. Methods: We isolated bona fide Tregs from expansion cultures based on their selective surface expression of latency-associated peptide (LAP). The TCR Vβ diversity and intracellular cytokine production of Tregs were determined by flow cytometer. The TSDR methylation was determined by epigenetic human FOXP3 qPCR Assay. Their in vitro and in vivo potency was confirmed with suppression assay and humanized xenogeneic GVHD (xGVHD) murine model, respectively. Results: LAP+ repurification results in >90% LAP+FOXP3+ Tregs, leaving behind FOXP3- and FOXP3+ nonTregs within the LAP- population. After 4-week expansion, the LAP+ Tregs were >1 billion cells, highly suppressive and anergic in vitro, >90% demethylated in the TSDR and able to maintain TCR Vβ diversity. In the xGVHD model, exogenous CD25-PBMC administered alone results in a median survival of 32 days. The co-transfer of LAP+ Tregs increased median survival to 47 days, while the LAP parent (CD25+) and LAP- nonTregs had median survival of 39 and 31 days, respectively. Conclusions: These preclinical data together provide evidence that LAP+ Tregs are highly purified with fully suppressive function for cell therapy. This population results in a more effective and safer product for immunotherapy to treat GVHD and provides the necessary preclinical data for transition into a clinical trial with LAP+ Tregs to prevent or treat GVHD and other autoimmune diseases.


Interleukin-18 as a predictor of future events in patients with acute coronary syndromes.
The aim of this study was to assess the short- and long-term prognostic significance of interleukin-18 (IL-18) levels in patients with acute coronary syndromes (ACS). In patients hospitalized with ACS (median age, 66 years; 30% females), we evaluated associations of serum IL-18 levels from day 1 (n=1261) with the short- (<3 months) and long-term (median, 7.6 years) risk of death, development of congestive heart failure (CHF), and myocardial infarction (MI). IL-18 was not significantly associated with short-term mortality. In the long term, IL-18 levels were significantly related to all-cause mortality, even after adjustment for clinical confounders (hazard ratio [HR], 1.19; 95% confidence interval, 1.07 to 1.33; P=0.002). Long-term, cardiovascular mortality was univariately related to IL-18, and the adjusted relation between noncardiovascular mortality and IL-18 was highly significant (HR, 1.36; 95% confidence interval, 1.11 to 1.67; P=0.003). IL-18 independently predicted CHF, MI, and cardiovascular death/CHF/MI in both the short and long term. Measurements from day 1 of ACS and 3 months after ACS had a similar power to predict late outcome. The addition of the measurement of IL-18 to clinical variables improved the prediction of risk of all-cause and noncardiovascular mortality. The association between IL-18 and noncardiovascular mortality is intriguing and warrants further study.


Superglue injuries of the eye.
To report various ocular lesions caused by accidental instillation of superglue. Three cases of ocular injuries are described in children aged 6 years, 3 years and 8 months, following accidental instillation of superglue in the eye. In the first case there was sticking of eyelashes in the medial 1/3 of eyelids in both eyes. In the second case sticking of eye lashes was present in the lateral 1/3 of eyelids in the left eye. In the third case, superglue was present on the right cheek, above the right ear and sticking of eyelids in medial 1/3 in right eye. The eyelids were separated by pulling the lid margins with fingers in the first case and later on superglue was removed by trimming the eyelashes; and by direct trimming the eyelashes in second and third cases. There was no injury to other structures of anterior segment in the first two cases. However, removal of the superglue on the cornea resulted in corneal abrasion in the third case which healed with medical treatment and patching of the right eye. Accidental instillation of superglue is possible because of the appearance of the tube like eye ointment tube. Immediate medical aid will prevent ocular morbidity.


Evaluation of a novel device for measuring patient compliance with oral appliances in the treatment of obstructive sleep apnea.
The purpose of this study was to evaluate a novel intraoral monitor for measuring patient compliance of oral appliances for the treatment of obstructive sleep apnea. A clinical trial was conducted to compare objective recording by an intraoral compliance monitor and self-reporting by participants using a mandibular repositioning device (MRD). Ten participants were fitted with a Thornton Adjustable Positioner (TAP III) with an embedded compliance monitor. The participants were asked to wear the test appliance for seven nights and to record their usage of the appliance and any adverse effects in a treatment journal. The data were downloaded to a dedicated computer using radio-frequency identification (RFID) technology, and the information was compared to the data in the participant's journal. The mean objective wearing time, as detected by the compliance monitor, was found to be 6.6 ± 1.6 hours/night. The mean subjective wearing time, as recorded by the participants, was 6.5 ± 1.5 hours/night. The correlation between subjective and objective times was 0.9985. The use of the test appliance by this sample population was 68.7% with a range of 24% to 100%. Participants reported a range of adverse outcomes related to the MRD consistent with those reported in the literature and were found to be transient in nature. This study supports previously reported usage times and adverse outcomes. The compliance monitor showed a very high linear correlation between subjective and objective data, validating its use in future compliance studies.


Hail detection with a differential reflectivity radar.
A major objective in the remote sensing of convective storms by radar is the clear and reliable differentiation between regions of hail and regions of rainfall. This report describes the application of the differential reflectivity (Z(DR)) radar technique to the problem of hail detection. The procedure is based on the markedly different polarization-dependent backscatter characteristics of rain and hail. Field experiments conducted in Colorado during the spring of 1983 provide significant evidence of hail detection with this new radar technique.


Structure-activity relationships and molecular modeling of 1,2,4-triazoles as adenosine receptor antagonists.
The structure-activity relationship (SAR) for a novel class of 1,2,4-triazole antagonists of the human A(2A) adenosine receptor (hA(2A)AR) was explored. Thirty-three analogs of a ligand that was discovered in a structure-based virtual screen against the hA(2A)AR were tested in hA(1), A(2A), and A(3) radioligand binding assays and in functional assays for the A(2B)AR subtype. As a series of closely related analogs of the initial lead, 1, did not display improved binding affinity or selectivity, molecular docking was used to guide the selection of more distantly related molecules. This resulted in the discovery of 32, a hA(2A)AR antagonist (K(i) 200 nM) with high ligand efficiency. In the light of the SAR for the 1,2,4-triazole scaffold, we also investigated the binding mode of these compounds based on docking to several A(2A)AR crystal structures.


Obtaining consensus in psychotherapy: What holds us back?
Although the field of psychotherapy has been in existence for well over a century, it nonetheless continues to be preparadigmatic, lacking a consensus or scientific core. Instead, it is characterized by a large and increasing number of different schools of thought. In addition to the varying ways in which psychotherapy has been conceptualized, there also exists a long-standing gap between psychotherapy research and how it is conducted in actual clinical practice. Finally, there also exists a tendency to place great emphasis on what is new, often rediscovering or reinventing past contributions. This article describes each of these impediments to obtaining consensus and offers some suggestions for what might be done to address them. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial.
Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol). Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks, followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day. Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation. The primary endpoint was time to culture conversion in liquid media within 12 weeks. Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis (modified intention to treat). Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables. The proportional hazard assumption was tested using Schoelfeld residuals, with threshold p<0·05 for non-proportionality. The trial is registered with ClinicalTrials.gov (NCT01785186). Between May 7, 2013, and March 25, 2014, we enrolled and randomly assigned 365 patients to different treatment arms (63 to rifampicin 35 mg/kg, isoniazid, pyrazinamide, and ethambutol; 59 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, SQ109; 57 to rifampicin 20 mg/kg, isoniazid, pyrazinamide, and SQ109; 63 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, and moxifloxacin; and 123 to the control arm). Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis. Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group (median 48 days vs 62 days, adjusted hazard ratio 1·78; 95% CI 1·22-2·58, p=0·003), but not in other experimental arms. There was no difference in any of the groups in time to culture conversion on solid media. 11 patients had treatment failure or recurrent disease during post-treatment follow-up: one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm. 45 (12%) of 365 patients reported grade 3-5 adverse events, with similar proportions in each arm. A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens. Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost. The study was funded by the European and Developing Countries Clinical Trials partnership (EDCTP), the German Ministry for Education and Research (BmBF), and the Medical Research Council UK (MRC).


Reversal of pentylenetetrazole-altered swimming and neural activity-regulated gene expression in zebrafish larvae by valproic acid and valerian extract.
Ethnopharmacology has documented hundreds of psychoactive plants awaiting exploitation for drug discovery. A robust and inexpensive in vivo system allowing systematic screening would be critical to exploiting this knowledge. The objective of this study was to establish a cheap and accurate screening method which can be used for testing psychoactive efficacy of complex mixtures of unknown composition, like plant crude extracts. We used automated recording of zebrafish larval swimming behavior during light vs. dark periods which we reproducibly altered with an anxiogenic compound, pentylenetetrazole (PTZ). First, we reversed this PTZ-altered swimming by co-treatment with a well-defined synthetic anxiolytic drug, valproic acid (VPA). Next, we aimed at reversing it by adding crude root extracts of Valeriana officinalis (Val) from which VPA was originally derived. Finally, we assessed how expression of neural activity-regulated genes (c-fos, npas4a, and bdnf) known to be upregulated by PTZ treatment was affected in the presence of Val. Both VPA and Val significantly reversed the PTZ-altered swimming behaviors. Noticeably, Val at higher doses was affecting swimming independently of the presence of PTZ. A strong regulation of all three neural-activity genes was observed in Val-treated larvae which fully supported the behavioral results. We demonstrated in a combined behavioral-molecular approach the strong psychoactivity of a natural extract of unknown composition made from V. officinalis. Our results highlight the efficacy and sensitivity of such an approach, therefore offering a novel in vivo screening system amenable to high-throughput testing of promising ethnobotanical candidates.


Relationships among pain disability, pain intensity, illness intrusiveness, and upper extremity disability in patients with traumatic peripheral nerve injury.
In patients with a peripheral nerve injury, a simple conceptualization assumes that pain disability is determined by pain intensity. This study evaluated the relationships among pain intensity, illness intrusiveness, and pain disability. After we obtained ethics board approval, we enrolled English-speaking adult patients who had experienced an upper extremity peripheral nerve injury 0.5 to 15 years previously. Patients completed the Disabilities of the Arm, Shoulder, and Hand (DASH), Illness Intrusiveness Scale, Pain Disability Index, and McGill Pain questionnaires. We used multivariate linear regression to evaluate the variables that predicted pain disability. There were 124 patients (41 women, 83 men; mean ± SD, 41 ± 16 y of age). The median time since injury was 14 months (range, 6-145 months), and there were 43 brachial plexus nerve injuries. Mean ± SD scores were: pain disability, 29 ± 18; illness intrusiveness, 40 ± 18; DASH, 45 ± 22; and pain intensity, 4.6 ± 3.0. The pain disability, DASH, and illness intrusiveness scores were significantly higher in patients with brachial plexus injuries than in those with distal nerve injuries (p<.05). There was strong correlation between pain disability and DASH (r = 0.764, p<.001) and illness intrusiveness (r = 0.738, p<.001) and a weaker correlation with pain intensity (r = 0.549, p<.001). The final regression model predicting pain disability scores explained 70% of the variance with these predictors: DASH (β = 0.452, p<.001), illness intrusiveness (β = 0.372, p<.001), and pain intensity (β = 0.143, p=.018). Pain disability was substantial after nerve injury, and pain intensity explained the least variance among the model variables. Pain intensity should be considered only one component of pain, and the impact of pain in the context of disability should be considered in patients with chronic nerve injury. Prognostic IV.


Interuncal distance measurements in healthy volunteers and in patients with Alzheimer disease.
To evaluate further the clinical utility of the interuncal distance (IUD) measured from axial MR scans as a reflection of hippocampal atrophy. The IUD measured from the axial MR scans of 17 healthy control subjects was correlated with the volume of the amygdala hippocampal complex obtained from coronal MR images. The IUD was also measured on axial MR scans in 12 patients with possible or probable Alzheimer disease. The correlation between the total amygdala hippocampal volume and the IUD was insignificant for control subjects (r = -0.38, P = .13). When analysis of covariance was performed with the IUD as the dependent variable and age and diagnosis as the independent variables, overall R2 was 0.25. Age (F = 5.02, df = 1, P = .034), but not diagnosis (F = 0.02, df = 2, P = .88), had a significant effect. The IUD has no significant correlation with the amygdala hippocampal volume. The IUD appears to be a better measure of overall brain volume, which changes with age. In our patient population diagnosed with mild to moderate Alzheimer disease, the IUD measurement was not found to be useful in distinguishing their scans from those of the volunteers.


The role of action representations in thematic object relations.
A number of studies have explored the role of associative/event-based (thematic) and categorical (taxonomic) relations in the organization of object representations. Recent evidence suggests that thematic information may be particularly important in determining relationships between manipulable artifacts. However, although sensorimotor information is on many accounts an important component of manipulable artifact representations, little is known about the role that action may play during the processing of semantic relationships (particularly thematic relationships) between multiple objects. In this study, we assessed healthy and left hemisphere stroke participants to explore three questions relevant to object relationship processing. First, we assessed whether participants tended to favor thematic relations including action (Th+A, e.g., wine bottle-corkscrew), thematic relationships without action (Th-A, e.g., wine bottle-cheese), or taxonomic relationships (Tax, e.g., wine bottle-water bottle) when choosing between them in an association judgment task with manipulable artifacts. Second, we assessed whether the underlying constructs of event relatedness, action relatedness, and categorical relatedness determined the choices that participants made. Third, we assessed the hypothesis that degraded action knowledge and/or damage to temporo-parietal cortex, a region of the brain associated with the representation of action knowledge, would reduce the influence of action on the choice task. Experiment 1 showed that explicit ratings of event, action, and categorical relatedness were differentially predictive of healthy participants' choices, with action relatedness determining choices between Th+A and Th-A associations above and beyond event and categorical ratings. Experiment 2 focused more specifically on these Th+A vs. Th-A choices and demonstrated that participants with left temporo-parietal lesions, a brain region known to be involved in sensorimotor processing, were less likely than controls and tended to be less likely than patients with lesions sparing that region to use action relatedness in determining their choices. These data indicate that action knowledge plays a critical role in processing of thematic relations for manipulable artifacts.


Evaluation of arterial stiffness for predicting future cardiovascular events in patients with ST segment elevation and non-ST segment elevation myocardial infarction.
Arterial stiffness parameters in patients who experienced MACE after acute MI have not been studied sufficiently. We investigated arterial stiffness parameters in patients with ST segment elevation (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI). Ninety-four patients with acute MI (45 STEMI and 49 NSTEMI) were included in the study. Arterial stiffness was assessed noninvasively by using TensioMed Arteriograph. Arterial stiffness parameters were found to be higher in NSTEMI group but did not achieve statistical significance apart from pulse pressure (P = 0.007). There was no significant difference at MACE rates between two groups. Pulse pressure and heart rate were also significantly higher in MACE observed group. Aortic pulse wave velocity (PWV), aortic augmentation index (AI), systolic area index (SAI), heart rate, and pulse pressure were higher; ejection fraction, the return time (RT), diastolic reflex area (DRA), and diastolic area index (DAI) were significantly lower in patients with major cardiovascular events. However, PWV, heart rate, and ejection fraction were independent indicators at development of MACE. Parameters of arterial stiffness and MACE rates were similar in patients with STEMI and NSTEMI in one year followup. The independent prognostic indicator aortic PWV may be an easy and reliable method for determining the risk of future events in patients hospitalized with acute MI.


A subacute toxicity evaluation of green tea (Camellia sinensis) extract in mice.
Green tea is believed to be beneficial to health because it possesses antioxidant, antiviral and anticancer properties. The potential toxicity of green tea when administered at high doses via concentrated extracts, however, has not been completely investigated. The objective of the present study was to evaluate the safety of green tea extract in ICR mice using a subacute exposure paradigm. In this study, mice were orally administered (gavage) green tea extract at doses of 0 (as normal group), 625, 1250 and 2500mg/kgbody weight/day for 28days. The results showed that oral administration of green tea extract did not cause adverse effects on body weight, organ weights, hematology, serum biochemistry, urinalysis or histopathology. Additionally, administering green tea extract via gavage significantly reduced triglyceride and cholesterol levels. These observed effects could be attributed to the high levels of catechins present in green tea as these compounds have been reported to have beneficial health effects. The no-observed-adverse-effect level for green tea extract derived from the results of the present study was 2500mg/kgbody weight/day.


Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.
Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation.